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Volume 63, Issue 2

infection induces vascular smooth muscle cell migration via Rac1 activation Free

Abstract

infection has been shown to be associated with the development of atherosclerosis by promoting the migration of vascular smooth muscle cells (VSMCs). However, how infection induces VSMC migration is not fully understood. A primary role of Ras-related C3 botulinum toxin substrate 1 (Rac1) is to generate a protrusive force at the leading edge that contributes to cell migration. Whether Rac1 activation plays a role in infection-induced VSMC migration is not well defined. In the present study, we therefore examined Rac1 activation in infected rat primary VSMCs and the role of Rac1 activation in infection-induced VSMC migration. Glutathione -transferase pull-down assay results showed that Rac1 was activated in -infected rat primary VSMCs. A Rac1 inhibitor, NSC23766 (50 µM,) suppressed Rac1 activation stimulated by infection, and thereby inhibited infection-induced VSMC migration. In addition, infection-induced Rac1 activation in the VSMCs was blocked by LY294002 (25 µM), an inhibitor of phosphatidylinositol 3-kinase (PI3K). Taken together, these data suggest that infection promotes VSMC migration, possibly through activating Rac1 via PI3K.

  • Received:
  • Accepted:
  • Published Online:
© 2014 SGM
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/content/journal/jmm/10.1099/jmm.0.065359-0
2014-02-01
2024-04-19
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References

  1. Akunuru S., Palumbo J., Zhai Q. J., Zheng Y. 2011; Rac1 targeting suppresses human non-small cell lung adenocarcinoma cancer stem cell activity. PLoS ONE 6:e16951 [View Article][PubMed]
     [Google Scholar]
  2. Bishop A. L., Hall A. 2000; Rho GTPases and their effector proteins. Biochem J 348:241–255 [View Article][PubMed]
     [Google Scholar]
  3. Brachmann S. M., Yballe C. M., Innocenti M., Deane J. A., Fruman D. A., Thomas S. M., Cantley L. C. 2005; Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement. Mol Cell Biol 25:2593–2606 [View Article][PubMed]
     [Google Scholar]
  4. Brantley-Sieders D. M., Caughron J., Hicks D., Pozzi A., Ruiz J. C., Chen J. 2004; EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation. J Cell Sci 117:2037–2049 [View Article][PubMed]
     [Google Scholar]
  5. Brown M. D., Bry L., Li Z., Sacks D. B. 2008; Actin pedestal formation by enteropathogenic Escherichia coli is regulated by IQGAP1, calcium, and calmodulin. J Biol Chem 283:35212–35222 [View Article][PubMed]
     [Google Scholar]
  6. Chen Q., Zhu Y. C., Yu J., Miao S., Zheng J., Xu L., Zhou Y., Li D., Zhang C. other authors 2010a; CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling. J Neurosci 30:12777–12786 [View Article][PubMed]
     [Google Scholar]
  7. Chen S., Shimada K., Zhang W., Huang G., Crother T. R., Arditi M. 2010b; IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae infection-accelerated atherosclerosis in mice. J Immunol 185:5619–5627 [View Article][PubMed]
     [Google Scholar]
  8. Choi K. H., Kim J. E., Song N. R., Son J. E., Hwang M. K., Byun S., Kim J. H., Lee K. W., Lee H. J. 2010; Phosphoinositide 3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells. Cardiovasc Res 85:836–844 [View Article][PubMed]
     [Google Scholar]
  9. Dawes A. T., Edelstein-Keshet L. 2007; Phosphoinositides and Rho proteins spatially regulate actin polymerization to initiate and maintain directed movement in a one-dimensional model of a motile cell. Biophys J 92:744–768 [View Article][PubMed]
     [Google Scholar]
  10. De Laurentiis A., Pardo O. E., Palamidessi A., Jackson S. P., Schoenwaelder S. M., Reichmann E., Scita G., Arcaro A. 2011; The catalytic class I(A) PI3K isoforms play divergent roles in breast cancer cell migration. Cell Signal 23:529–541 [View Article][PubMed]
     [Google Scholar]
  11. Dechend R., Maass M., Gieffers J., Dietz R., Scheidereit C., Leutz A., Gulba D. C. 1999; Chlamydia pneumoniae infection of vascular smooth muscle and endothelial cells activates NF-kappaB and induces tissue factor and PAI-1 expression: a potential link to accelerated arteriosclerosis. Circulation 100:1369–1373 [View Article][PubMed]
     [Google Scholar]
  12. Dise R. S., Frey M. R., Whitehead R. H., Polk D. B. 2008; Epidermal growth factor stimulates Rac activation through Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 294:G276–G285 [View Article][PubMed]
     [Google Scholar]
  13. Eitel J., Meixenberger K., van Laak C., Orlovski C., Hocke A., Schmeck B., Hippenstiel S., N’Guessan P. D., Suttorp N., Opitz B. 2012; Rac1 regulates the NLRP3 inflammasome which mediates IL-1β production in Chlamydophila pneumoniae infected human mononuclear cells. PLoS ONE 7:e30379 [View Article][PubMed]
     [Google Scholar]
  14. Faroudi M., Hons M., Zachacz A., Dumont C., Lyck R., Stein J. V., Tybulewicz V. L. 2010; Critical roles for Rac GTPases in T-cell migration to and within lymph nodes. Blood 116:5536–5547 [View Article][PubMed]
     [Google Scholar]
  15. Fukata M., Watanabe T., Noritake J., Nakagawa M., Yamaga M., Kuroda S., Matsuura Y., Iwamatsu A., Perez F., Kaibuchi K. 2002; Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 109:873–885 [View Article][PubMed]
     [Google Scholar]
  16. Gaydos C. A., Summersgill J. T., Sahney N. N., Ramirez J. A., Quinn T. C. 1996; Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells. Infect Immun 64:1614–1620[PubMed]
     [Google Scholar]
  17. Gouëffic Y., Guilluy C., Guérin P., Patra P., Pacaud P., Loirand G. 2006; Hyaluronan induces vascular smooth muscle cell migration through RHAMM-mediated PI3K-dependent Rac activation. Cardiovasc Res 72:339–348 [View Article][PubMed]
     [Google Scholar]
  18. Högdahl M., Söderlund G., Kihlström E. 2008; Expression of chemokines and adhesion molecules in human coronary artery endothelial cells infected with Chlamydia (Chlamydophila) pneumoniae . APMIS 116:1082–1088 [View Article][PubMed]
     [Google Scholar]
  19. Hu Z., Du J., Yang L., Zhu Y., Yang Y., Zheng D., Someya A., Gu L., Lu X. 2012; GEP100/Arf6 is required for epidermal growth factor-induced ERK/Rac1 signaling and cell migration in human hepatoma HepG2 cells. PLoS ONE 7:e38777 [View Article][PubMed]
     [Google Scholar]
  20. Huang Q., Shen H. M., Ong C. N. 2005; Emodin inhibits tumor cell migration through suppression of the phosphatidylinositol 3-kinase-Cdc42/Rac1 pathway. Cell Mol Life Sci 62:1167–1175 [View Article][PubMed]
     [Google Scholar]
  21. Konakahara S., Suzuki Y., Kawakami T., Saitou M., Kajikawa M., Masuho Y., Kohroki J. 2012; A neuronal transmembrane protein LRFN4 complexes with 14-3-3s and NCK1 to induce morphological change in monocytic cells via Rac1-mediated actin cytoskeleton reorganization. FEBS Lett 586:2251–2259 [View Article][PubMed]
     [Google Scholar]
  22. Kumerz M., Heiss E. H., Schachner D., Atanasov A. G., Dirsch V. M. 2011; Resveratrol inhibits migration and Rac1 activation in EGF- but not PDGF-activated vascular smooth muscle cells. Mol Nutr Food Res 55:1230–1236 [View Article][PubMed]
     [Google Scholar]
  23. Lai Y., Shen Y., Liu X. H., Zhang Y., Zeng Y., Liu Y. F. 2011; Interleukin-8 induces the endothelial cell migration through the activation of phosphoinositide 3-kinase-Rac1/RhoA pathway. Int J Biol Sci 7:782–791 [View Article][PubMed]
     [Google Scholar]
  24. Le Clainche C., Schlaepfer D., Ferrari A., Klingauf M., Grohmanova K., Veligodskiy A., Didry D., Le D., Egile C. other authors 2007; IQGAP1 stimulates actin assembly through the N-WASP-Arp2/3 pathway. J Biol Chem 282:426–435 [View Article][PubMed]
     [Google Scholar]
  25. Lin F. Y., Lin Y. W., Huang C. Y., Chang Y. J., Tsao N. W., Chang N. C., Ou K. L., Chen T. L., Shih C. M., Chen Y. H. 2011; GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, induces lectin-like oxidized low-density lipoprotein receptor 1 expression in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits. J Immunol 186:4405–4414 [View Article][PubMed]
     [Google Scholar]
  26. Liu R. Q., Yamamoto M., Moroi M., Kubota T., Ono T., Funatsu A., Komatsu H., Tsuji T., Hara H. other authors 2005; Chlamydia pneumoniae immunoreactivity in coronary artery plaques of patients with acute coronary syndromes and its relation with serology. Am Heart J 150:681–688 [View Article][PubMed]
     [Google Scholar]
  27. Luque A., Turu M. M., Rovira N., Juan-Babot J. O., Slevin M., Krupinski J. 2012; Early atherosclerotic plaques show evidence of infection by Chlamydia pneumoniae . Front Biosci (Elite Ed) 4:2423–2432 [View Article][PubMed]
     [Google Scholar]
  28. MacIntyre A., Abramov R., Hammond C. J., Hudson A. P., Arking E. J., Little C. S., Appelt D. M., Balin B. J. 2003; Chlamydia pneumoniae infection promotes the transmigration of monocytes through human brain endothelial cells. J Neurosci Res 71:740–750 [View Article][PubMed]
     [Google Scholar]
  29. Maddala R., Chauhan B. K., Walker C., Zheng Y., Robinson M. L., Lang R. A., Rao P. V. 2011; Rac1 GTPase-deficient mouse lens exhibits defects in shape, suture formation, fiber cell migration and survival. Dev Biol 360:30–43[PubMed] [CrossRef]
     [Google Scholar]
  30. Makrodouli E., Oikonomou E., Koc M., Andera L., Sasazuki T., Shirasawa S., Pintzas A. 2011; BRAF and RAS oncogenes regulate Rho GTPase pathways to mediate migration and invasion properties in human colon cancer cells: a comparative study. Mol Cancer 10:118 [View Article][PubMed]
     [Google Scholar]
  31. Meng D., Lv D. D., Fang J. 2008; Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells. Cardiovasc Res 80:299–308 [View Article][PubMed]
     [Google Scholar]
  32. Migeotte I., Grego-Bessa J., Anderson K. V. 2011; Rac1 mediates morphogenetic responses to intercellular signals in the gastrulating mouse embryo. Development 138:3011–3020 [View Article][PubMed]
     [Google Scholar]
  33. Raftopoulou M., Hall A. 2004; Cell migration: Rho GTPases lead the way. Dev Biol 265:23–32 [View Article][PubMed]
     [Google Scholar]
  34. Schmidt R., Redecke V., Breitfeld Y., Wantia N., Miethke T., Massberg S., Fischel S., Neumann F. J., Schömig A., May A. E. 2006; EMMPRIN (CD 147) is a central activator of extracellular matrix degradation by Chlamydia pneumoniae-infected monocytes. Implications for plaque rupture. Thromb Haemost 95:151–158[PubMed]
     [Google Scholar]
  35. Subtil A., Wyplosz B., Balañá M. E., Dautry-Varsat A. 2004; Analysis of Chlamydia caviae entry sites and involvement of Cdc42 and Rac activity. J Cell Sci 117:3923–3933 [View Article][PubMed]
     [Google Scholar]
  36. Tang M. C., Chan L. C., Yeh Y. C., Chen C. Y., Chou T. Y., Wang W. S., Su Y. 2011; Thymosin beta 4 induces colon cancer cell migration and clinical metastasis via enhancing ILK/IQGAP1/Rac1 signal transduction pathway. Cancer Lett 308:162–171 [View Article][PubMed]
     [Google Scholar]
  37. Tscharntke M., Pofahl R., Chrostek-Grashoff A., Smyth N., Niessen C., Niemann C., Hartwig B., Herzog V., Klein H. W. other authors 2007; Impaired epidermal wound healing in vivo upon inhibition or deletion of Rac1. J Cell Sci 120:1480–1490 [View Article][PubMed]
     [Google Scholar]
  38. Uriarte S. M., Molestina R. E., Miller R. D., Bernabo J., Farinati A., Eiguchi K., Ramirez J. A., Summersgill J. T. 2004; Effects of fluoroquinolones on the migration of human phagocytes through Chlamydia pneumoniae-infected and tumor necrosis factor alpha-stimulated endothelial cells. Antimicrob Agents Chemother 48:2538–2543 [View Article][PubMed]
     [Google Scholar]
  39. Verkhovsky A. B., Chaga O. Y., Schaub S., Svitkina T. M., Meister J. J., Borisy G. G. 2003; Orientational order of the lamellipodial actin network as demonstrated in living motile cells. Mol Biol Cell 14:4667–4675 [View Article][PubMed]
     [Google Scholar]
  40. Wang B. B., Zhang L. J., Zhang T. T., Wang H. W., Zhang J. X., Wei J. Y., Shen B. L., Liu X., Xu Z. L., Zhang L. J. 2013; Chlamydia pneumoniae infection promotes vascular smooth muscle cell migration through Toll-like receptor 2-related signaling pathway. Infect Immun 81:4583–4591 [View Article][PubMed]
     [Google Scholar]
  41. Welf E. S., Ahmed S., Johnson H. E., Melvin A. T., Haugh J. M. 2012; Migrating fibroblasts reorient directionality by a metastable, PI3K-dependent mechanism. J Cell Biol 197:105–114 [View Article][PubMed]
     [Google Scholar]
  42. Zhang L. J., Zhang L. J., Quan W., Wang B. B., Shen B. L., Zhang T. T., Kang Y. 2011; Berberine inhibits HEp-2 cell invasion induced by Chlamydophila pneumoniae infection. J Microbiol 49:834–840 [View Article][PubMed]
     [Google Scholar]
  43. Zhang L. J., Li X. K., Zhang L. J., Wang B. B., Zhang T. T., Ye J. 2012; Chlamydophila (Chlamydia) pneumoniae infection promotes vascular smooth muscle cell adhesion and migration through IQ domain GTPase-activating protein 1. Microb Pathog 53:207–213 [View Article][PubMed]
     [Google Scholar]
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Chlamydia pneumoniae infection induces vascular smooth muscle cell migration via Rac1 activation
J. Med. Microbiol. 63, 155 (2014); https://doi.org/10.1099/jmm.0.065359-0
/content/journal/jmm/10.1099/jmm.0.065359-0
/content/journal/jmm/10.1099/jmm.0.065359-0
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